Flashcards in Lec 55: Pharmacokinetics I Deck (12):

1

## Zero order kinetics

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constant rate of absorption or elimination

-LINEAR, M=kt

-speed is constant, rate of absorptionis independent of concentration gradient

-transport mechanism is saturated

2

## First order kinetics

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-rate is proportional to the amount of drug still unabsorbed

-EXPONENTIAL, M= Mo(e)^(-kt)

-increase difference:increase speed

-[ ] is major determinant, gradient counts!

-not constant amount, constant fraction

3

##
order Applications: Drug Absorption/Drug Elimination

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zero order elimination - duration of a therapeutically effective drug [] increases linearly with amount in body fluids

first order elimination - duration of a therapeutically effective drug [] increases as the log of the amount in the body fluids does

4

## half life equation

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half life = 0.693/ke

ke=rate constant of elimination

5

## Volume of Distribution

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-apparent Volume in which the drug is distributed (a concept, not a real number)

Vd=(mg drug in body)/([]in plasma mg/L)

-as plasma [] decreases, Vd increases

-can be much higher than the total body volume if drug is nonhomogenously distributed with high [] in extravasculartissues (plasma [ ] is low in this case)

6

## Clearance

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-expressed in L/hr or mL/min

-Volume of plasma cleared of drug

-CL is additive

CL=(rate of elimination in mg/hr)/([] drug in mg/L)

CL=(ke)*(Vd)

half life=0.693*Vd/CL

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## Bioavailability

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-fraction of unchanged drug reaching systemic circulation after oral administation (F)

F=f(1-ER)

ER= extraction ration in liver

f=fraction absorbed from gut

8

## Extent of absorption

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ratio of drug entering blood circulation to total drug in digestive system

rate= extent *time

9

## First Pass Elimination

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presystemic hepatic elimination; passes through liver before system circulation and may be metabolized or excreted into bile

-drug is decreased by : QCi - QCo, where Q= 90 L/h hepatic blood flow and Ci=drug entering liver, and Co = drug leaving

Hepatic CL= Q*ER

***if ER is large, we can compensate for low oral bioavailability by 1) increasing dose and 2) use alternative administative routes

10

##
accumulation factor of a drug when the dosing interval is shorter than four half-live

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accumulation factor = 1/(fraction lost in one dosing interval)

example: for a drug given once every half life, AF=2

11

## Dosing Regimen Construction

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1.identify target [] that will produce desired effect - [] range between that causing ½ of greatest therapeutic effect (lower limit) and [] that will cause side effects in no more than 5-10% of all patients (uppe rlimit)

2.determine Vd and CL

3.maintenance dose

a.dosing rate = CL*Css , where Css= []at steady state

4.if intermittent doses are given, then maintenance dose is determined by:maintenance dose=dosing rate* dosing interval

5.if target [] needs to be reached quick, and or elimination rate ke is small, loading doses might be applied: loading dose= Vd*Target []

6.check for desired effect and adjust

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